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Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients

Pancreatic cancer remains among the most lethal cancers worldwide, with poor early detection rates and poor survival rates. Patient-derived xenograft (PDX) models have increasingly been used in preclinical and clinical research of solid cancers to fulfil unmet need. Fresh tumour samples from human p...

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Autores principales: Roche, Sandra, O’Neill, Fiona, Murphy, Jean, Swan, Niall, Meiller, Justine, Conlon, Neil T., Geoghegan, Justin, Conlon, Kevin, McDermott, Ray, Rahman, Rozana, Toomey, Sinead, Straubinger, Ninfa L., Straubinger, Robert M., O’Connor, Robert, McVey, Gerard, Moriarty, Michael, Clynes, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037178/
https://www.ncbi.nlm.nih.gov/pubmed/32024004
http://dx.doi.org/10.3390/ijms21030962
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author Roche, Sandra
O’Neill, Fiona
Murphy, Jean
Swan, Niall
Meiller, Justine
Conlon, Neil T.
Geoghegan, Justin
Conlon, Kevin
McDermott, Ray
Rahman, Rozana
Toomey, Sinead
Straubinger, Ninfa L.
Straubinger, Robert M.
O’Connor, Robert
McVey, Gerard
Moriarty, Michael
Clynes, Martin
author_facet Roche, Sandra
O’Neill, Fiona
Murphy, Jean
Swan, Niall
Meiller, Justine
Conlon, Neil T.
Geoghegan, Justin
Conlon, Kevin
McDermott, Ray
Rahman, Rozana
Toomey, Sinead
Straubinger, Ninfa L.
Straubinger, Robert M.
O’Connor, Robert
McVey, Gerard
Moriarty, Michael
Clynes, Martin
author_sort Roche, Sandra
collection PubMed
description Pancreatic cancer remains among the most lethal cancers worldwide, with poor early detection rates and poor survival rates. Patient-derived xenograft (PDX) models have increasingly been used in preclinical and clinical research of solid cancers to fulfil unmet need. Fresh tumour samples from human pancreatic adenocarcinoma patients were implanted in severe combined immunodeficiency (SCID) mice. Samples from 78% of treatment-naïve pancreatic ductal adenocarcinoma patients grew as PDX tumours and were confirmed by histopathology. Frozen samples from F1 PDX tumours could be later successfully passaged in SCID mice to F2 PDX tumours. The human origin of the PDX was confirmed using human-specific antibodies; however, the stromal component was replaced by murine cells. Cell lines were successfully developed from three PDX tumours. RNA was extracted from eight PDX tumours and where possible, corresponding primary tumour (T) and adjacent normal tissues (N). mRNA profiles of tumour vs. F1 PDX and normal vs. tumour were compared by Affymetrix microarray analysis. Differential gene expression showed over 5000 genes changed across the N vs. T and T vs. PDX samples. Gene ontology analysis of a subset of genes demonstrated genes upregulated in normal vs. tumour vs. PDX were linked with cell cycle, cycles cell process and mitotic cell cycle. Amongst the mRNA candidates elevated in the PDX and tumour vs. normal were SERPINB5, FERMT1, AGR2, SLC6A14 and TOP2A. These genes have been associated with growth, proliferation, invasion and metastasis in pancreatic cancer previously. Cumulatively, this demonstrates the applicability of PDX models and transcriptomic array to identify genes associated with growth and proliferation of pancreatic cancer.
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spelling pubmed-70371782020-03-11 Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients Roche, Sandra O’Neill, Fiona Murphy, Jean Swan, Niall Meiller, Justine Conlon, Neil T. Geoghegan, Justin Conlon, Kevin McDermott, Ray Rahman, Rozana Toomey, Sinead Straubinger, Ninfa L. Straubinger, Robert M. O’Connor, Robert McVey, Gerard Moriarty, Michael Clynes, Martin Int J Mol Sci Article Pancreatic cancer remains among the most lethal cancers worldwide, with poor early detection rates and poor survival rates. Patient-derived xenograft (PDX) models have increasingly been used in preclinical and clinical research of solid cancers to fulfil unmet need. Fresh tumour samples from human pancreatic adenocarcinoma patients were implanted in severe combined immunodeficiency (SCID) mice. Samples from 78% of treatment-naïve pancreatic ductal adenocarcinoma patients grew as PDX tumours and were confirmed by histopathology. Frozen samples from F1 PDX tumours could be later successfully passaged in SCID mice to F2 PDX tumours. The human origin of the PDX was confirmed using human-specific antibodies; however, the stromal component was replaced by murine cells. Cell lines were successfully developed from three PDX tumours. RNA was extracted from eight PDX tumours and where possible, corresponding primary tumour (T) and adjacent normal tissues (N). mRNA profiles of tumour vs. F1 PDX and normal vs. tumour were compared by Affymetrix microarray analysis. Differential gene expression showed over 5000 genes changed across the N vs. T and T vs. PDX samples. Gene ontology analysis of a subset of genes demonstrated genes upregulated in normal vs. tumour vs. PDX were linked with cell cycle, cycles cell process and mitotic cell cycle. Amongst the mRNA candidates elevated in the PDX and tumour vs. normal were SERPINB5, FERMT1, AGR2, SLC6A14 and TOP2A. These genes have been associated with growth, proliferation, invasion and metastasis in pancreatic cancer previously. Cumulatively, this demonstrates the applicability of PDX models and transcriptomic array to identify genes associated with growth and proliferation of pancreatic cancer. MDPI 2020-01-31 /pmc/articles/PMC7037178/ /pubmed/32024004 http://dx.doi.org/10.3390/ijms21030962 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Roche, Sandra
O’Neill, Fiona
Murphy, Jean
Swan, Niall
Meiller, Justine
Conlon, Neil T.
Geoghegan, Justin
Conlon, Kevin
McDermott, Ray
Rahman, Rozana
Toomey, Sinead
Straubinger, Ninfa L.
Straubinger, Robert M.
O’Connor, Robert
McVey, Gerard
Moriarty, Michael
Clynes, Martin
Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients
title Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients
title_full Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients
title_fullStr Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients
title_full_unstemmed Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients
title_short Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients
title_sort establishment and characterisation by expression microarray of patient-derived xenograft panel of human pancreatic adenocarcinoma patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037178/
https://www.ncbi.nlm.nih.gov/pubmed/32024004
http://dx.doi.org/10.3390/ijms21030962
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